Fimasartan is known as an angiotensin II receptor antagonist developed for the treatment of hypertension and other medical indications (Korean Patent No. 10-1058284), Fimasartan is chemically defined as 2-n-butyl-5-dimethylaminothiocarbonylmethyl-6-methyl-3-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]pyrimidin-4(3H)-one, is a nonpeptide molecular-chemically defined, and has an empirical formula of C27H30N7OS and a molecular weight of 501.65. Fimasartan has been approved as a pharmaceutical product, fimasartan potassium trihydrate, for use in South Korea and commercially available.
Moreover, hydrochlorothiazide is a diuretic that is orally administered for the treatment of edema and hypertension and has a chemical name of 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide, an empirical formula of C7H8ClN3O4S2, and a molecular weight of 297.74.
The combination therapy with an ARB drug including fimasartan, and hydrochlorothiazide as a diuretic, has been known to exhibit synergistic therapeutic efficacy in the treatment of hypertension, and thus many studies have been conducted to structurally combine the ARB drug and the diuretic hydrochlorothiazide, but it is difficult to uniformly combine two drugs in pharmaceutical preparations.
When a product containing high contents of main components is prepared by mixing and direct tableting, tableting problems such as capping or sticking are generally caused by the properties of the main components. Fimasartan has high scattering properties due to its relatively low bulk and tapped densities and tends to agglomerate with each other. Due to its agglomerating properties, when fimasartan is mixed in a high share mixer, uniform mixing is very difficult to achieve. Moreover, there is a more than 10-fold difference in the mixing ratio of fimasartan and hydrochlorothiazide, and thus it is very difficult to prepare a granule in which the contents of two main components are uniform.
Therefore, there is a need to provide a pharmaceutical composition containing active ingredients of fimasartan and hydrochlorothiazide with excellent physical properties of granules for the preparation of tablets and high content uniformity of fimasartan and hydrochlorothiazide.